The central goal of this study is to describe and explain longitudinal patterns of adolescent substance use among sexual minority girls. Our meta-analysis of 18 cross-sectional studies showed that the odds of substance use for sexual minority girls were 400% higher than they were for heterosexual girls;However, few if any studies have examined longitudinal patterns of use, significant risk markers, mediators, or moderators of this disparity (Marshal et al., 2008). Only two studies to date have examined trajectories of substance use behavior among young sexual minority youth, and suggest that these disparities are maintained or increase over time as sexual minority youth approach young adulthood (Corliss et al., 2008;Marshal et al., 2009). Furthermore, cross-sectional evidence suggests that substance use among sexual minority girls is associated with other psychosocial health problems such as depression (Fergusson et al., 1999;Garofalo, et al., 1998). However no studies to date have examined the role of psychosocial risk factors in the long term patterns of substance use in this high risk population. We are proposing a developmental interpretation and application of Minority Stress Theory (MST;Hatzenbuehler, 2009;Meyer, 2003). Our new approach combines it with Developmental Psychopathology Theory (Cicchetti &Cohen, 2006) in order to articulate the unique needs and problems faced by sexual minority youth. Our Specific Aims are to: (1) Examine disparities between sexual minority girls and heterosexual girls in the age of onset and longitudinal course of substance use (quantity and frequency of cigarette, alcohol, and illicit drug use);(2) Determine whether the association between sexual minority status and trajectories of substance use is moderated or mediated by other psychosocial risk and protective factors (e.g., mental health, risky sexual behavior, deviant peer affiliation, victimization, social support, self-esteem, parent-child relationship quality);and (3) Explore whether the associations between sexual minority status, psychosocial factors, and substance use vary across demographic subgroups (e.g., age, ethnicity, family structure, SES). This proposal is innovative because: (1) it will be the first to characterize the onset, course, and long-term psychosocial correlates of substance use among sexual minority girls;(2) it will develop a new theoretical approach to describing and explaining risk for substance use among sexual minority youth;and we will (3) fill critical gaps in the health disparities and health services literatures, as well as provide important descriptive and explanatory information about longitudinal pathways of risk among this highly vulnerable group that will help inform future research, prevention, and intervention programs. PUBLIC HEALTH RELEVANCE: The primary goal of this study is to describe and explain longitudinal patterns of adolescent substance use among sexual minority girls. Recent meta-analysis results showed that the odds of adolescent substance use for sexual minority girls were 400% higher than they were for heterosexual girls. However, very few studies have examined longitudinal patterns of use, significant risk markers, mediators, or moderators of this disparity. This longitudinal study will characterize the onset, course, and long-term psychosocial risk and protective factors associated with substance use among sexual minority girls, and in doing so it will fill critical gaps in the health disparities and health services literatures.